High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures

© 2020, Minn et al..

During mammalian gastrulation, germ layers arise and are shaped into the body plan while extraembryonic layers sustain the embryo. Human embryonic stem cells, cultured with BMP4 on extracellular matrix micro-discs, reproducibly differentiate into gastruloids, expressing markers of germ layers and extraembryonic cells in radial arrangement. Using single-cell RNA sequencing and cross-species comparisons with mouse, cynomolgus monkey gastrulae, and post-implantation human embryos, we reveal that gastruloids contain cells transcriptionally similar to epiblast, ectoderm, mesoderm, endoderm, primordial germ cells, trophectoderm, and amnion. Upon gastruloid dissociation, single cells reseeded onto micro-discs were motile and aggregated with the same but segregated from distinct cell types. Ectodermal cells segregated from endodermal and extraembryonic but mixed with mesodermal cells. Our work demonstrates that the gastruloid system models primate-specific features of embryogenesis, and that gastruloid cells exhibit evolutionarily conserved sorting behaviors. This work generates a resource for transcriptomes of human extraembryonic and embryonic germ layers differentiated in a stereotyped arrangement.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:9

Enthalten in:

eLife - 9(2020) vom: 18. Nov.

Sprache:

Englisch

Beteiligte Personen:

Minn, Kyaw Thu [VerfasserIn]
Fu, Yuheng C [VerfasserIn]
He, Shenghua [VerfasserIn]
Dietmann, Sabine [VerfasserIn]
George, Steven C [VerfasserIn]
Anastasio, Mark A [VerfasserIn]
Morris, Samantha A [VerfasserIn]
Solnica-Krezel, Lilianna [VerfasserIn]

Links:

Volltext

Themen:

Amnion
BMP4 protein, human
Basic Helix-Loop-Helix Transcription Factors
Bone Morphogenetic Protein 4
Cell Adhesion Molecules
Cell sorting
Developmental biology
Gastrulation
Germ layers
Helix-loop-helix protein, eHAND
Human
Journal Article
Primordial germ cells
Regenerative medicine
Research Support, Non-U.S. Gov't
Stem cells
TFAP2A protein, human
Transcription Factor AP-2
Trophectoderm
WNT6 protein, human
Wnt Proteins

Anmerkungen:

Date Completed 16.03.2021

Date Revised 30.03.2024

published: Electronic

GEO: GSE144897, GSE130114, GSE74767, GSE125616, GSE136447, GSE75748, GSE85066, GSE109979, GSE140021, GSE134571

Citation Status MEDLINE

doi:

10.7554/eLife.59445

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM31773265X